This proposal is to investigate the long-term effects of androgen or estrogen on the development of rat prostate. The actions of these hormones during neonatal and/or weanling periods will be explored in depth. The relationship between hormonal condition during discrete developmental period and the induction of prostatic cancer will be emphasized. Specifically, the following studies will be performed. 1) To study the long-term effects of different hormonal conditions during neonatal and/or weanling periods on the development of prostate gland in intact rats. The differential effects of hormones on ventral and dorso-lateral lobes of rat prostate will be examined by morphological, histochemical and biochemical methods. 2) To study the synergistic effects of chemical carcinogens and hormonal imprinting on the development of rat prostate. Rat prostate will be exposed to a chemical carcinogen (3-methylcholanthrene or N-methyl-N-nitrosourea) either in vivo or in vitro and the effects of hormonal imprinting during neonatal and weanling period on the subsequent development of prostatic cancer will be investigated. 3) To determine whether the influence of hormonal conditions on prostatic development are direct or mediated via a generalized systemic programming of the host. This question will be resolved by utilizing the technique of tissue transplantation. Prostatic tissue from hormonal imprinted animal will be transplanted to a recipient host and the exhibition of certain imprinted characteristics in this tissue will be monitored. 4) To probe biochemical parameters that may be indicative of the development of prostatic cancer. We have developed a sensitive two-dimensional gel electrophoretic technique which can be used to analyze changes of tissue proteins during development. The question of whether hormone-induced cancer may relate to their stimulation of DNA synthesis in normal prostatic cells, shorten the life-span of these cells, and alter the cell population in favor of the "transformed" cells will be investigated.